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First published online 9 May 2006
doi: 10.1242/jcs.02932

Journal of Cell Science 119, 2204-2213 (2006)
Published by The Company of Biologists 2006
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Mesenchymal stem cells reside in virtually all post-natal organs and tissues

Lindolfo da Silva Meirelles, Pedro Cesar Chagastelles and Nance Beyer Nardi*

Departamento de Genética, Universidade Federal do Rio Grande do Sul, Av Bento Gonçalves 9500, 91540-970 Porto Alegre, RS, Brazil


Figure 1
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  		Fig. 1. Morphology of MSC cultures derived from different organs and tissues. (A) Phase-contrast micrographs of MSC-like cells in primary culture of aorta 24 hours after plating. Glomerulus outgrowth on the fourth (B) and sixth (C) day post-plating. (D) Heterogeneity among bone marrow-derived cells at passage 4, with MSC-like cells (lower portion), spindle-shaped and round cells. (E) Pancreas-derived MSCs at passage 30. (F) Vena-cava-derived MSCs at passage 22. Magnifications, x100 (B-F); x200 (A).

 

Figure 2
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  		Fig. 2. Immunophenotypic profile of MSCs derived from different sources. Flow cytometry histograms show the expression (shaded) of selected molecules (CD34, Sca-1, CD29, CD44, CD49e, CD90.2 and CD117) by different MSC populations compared with controls (unshaded peaks). Kidney-derived MSCs and kidney glomerulus-derived MSCs share essentially the same surface profile.

 

Figure 3
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  		Fig. 3. Effect of long-term culture on the expression of CD117, CD34, Sca-1 and CD49e. Thymus-derived MSCs were analyzed by flow cytometry at passages 11 and 42. Whereas the level of expression of Sca-1 was around 2 log values (versus 1 log control), CD117 expression decreased to nearly control levels, CD34 expression was lost, and expression of CD49e increased 1 log value.

 

Figure 4
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  		Fig. 4. {alpha}SMA expression by MSCs. The histograms represent levels of expression of {alpha}SMA (shaded) in MSCs from vena cava, bone marrow, muscle, pancreas and kidney glomeruli compared with controls (unshaded).

 

Figure 5
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  		Fig. 5. Comparative growth kinetics of cultures originated from different organs and tissues. Growth curves of representative MSC populations from each source (as presented in Table 1) are plotted. The threshold for 50 population doublings (50 Pds) is shown as a dashed line. Lowercase letters indicate the tissue or organ from which the culture was derived: a, aorta; b, brain; bm, bone marrow; k, kidney; l, liver; lu, lungs; m, muscle; p, pancreas; s, spleen; t, thymus; vc, vena cava. Numbers and capital letters refer to the animal used. Growth area is represented as a multiple of the area occupied by a confluent primary culture, arbitrarily set to 1.

 

Figure 6
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  		Fig. 6. Differentiation of MSCs derived from different sources, as presented in Table 1. MSCs were cultured in osteogenic or adipogenic medium for up to 2 months. Calcium deposited in the extracellular matrix is stained red by Alizarin Red S (A,C,E,G,I,K,M,O-Q,S). Lipid vacuoles are stained orange with Oil Red O (B,D,F,H,J,L,N,R,T). Magnifications and passage number (P) are indicated below each image. Cell lines are identified as described in the legend to Fig. 5.

 

Figure 7
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  		Fig. 7. Non-induced MSC differentiation in primary culture. Aorta primary cultures exhibit myogenic (A) and adipogenic (B) differentiation. The same happens in muscle primary cultures (C and D, respectively). Magnifications are indicated on each image.

 

Figure 8
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  		Fig. 8. A proposed model of MSC contribution to tissue maintenance. In this schematic representation of the transverse section of a simple vessel, MSCs lie in the basement membrane (red line), opposed to endothelial cells. Cues provided by the tissue-specific microenvironment coordinate a gradual transition (represented by green color gradient) from undifferentiated cells to progenitor and mature cell phenotypes. This process can occur naturally as represented by the dotted arrow (A). In case of tissue injury, undifferentiated MSCs can be mobilized directly into the tissue without the progenitor transition as represented by the curved arrow (B).

 




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